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Pangea Systems Uses Software To Design DNA Expression Chips For Hoechst-Ariad


OAKLAND, Calif.--Pangea Systems announced this month that its chip design software is being used by Hoechst Marion Roussel and the Hoechst-Ariad Genomics Center in Cambridge, Mass., to create custom Affymetrix gene expression chips from full-length sequences and clustered fragments of genes that the pharmaceutical company has identified.

Pangea said its tools automate the identification and selection of gene sequences for incorporation into custom DNA expression chips, rapidly producing error-free sequence sets in the appropriate format for chip manufacture. Pangea claimed its chip design software, which it currently offers as part of a service package, can, in just hours, automatically and more accurately accomplish the sort of sequence selection and design efforts that once required weeks of labor.

John Burke, a senior bioinformatics scientist for Pangea, called the software product "a highly automated way to produce sequence set designs for DNA chips." The sotware helps make, he said, "a highly curated chip with low noise and with a lot of error correction that produces a higher-quality result." Burke asserted that the product has the potential to make the design of custom arrays easier than ever.

Beyond clustering and alignment

Last fall, the Hoechst-Ariad Genomics Center licensed Pangea's expressed sequence tag (EST) clustering and alignment tools for use in its bioinformatics programs. John Couch, Pangea's president, said his company's chip design software amplifies the gains that the EST tools provide. "One component of the Pangea chip design tools automatically segregates and classifies gene isoforms and polymorphisms that may be linked to disease," Couch explained. For Hoechst, Pangea's tools automatically identified optimal regions for chip design and output results into a format developed by Affymetrix.

Burke explained that Hoe-chst initially licensed the Pan-gea tools in order to identify and validate targets. "The next process we wanted to focus on was moving these targets closer to the actual final validation or final therapy stage, where you use them to attack disease," Burke said.

Pangea's program "moves the straight target data into chip designs by selecting a unique sequence for each entry on a chip and ranking the priority of the target according to its membership in certain therapeutic programs and according to the source of the data," Burke added. For instance, he said, "certain targets might be of interest to a certain group in the company working on a particular disease, so that group might have highest priority. Also, if you're very confident of certain entries because you already have full-length sequences for them, you can assign high confidence to those."

Different chip modes

Pangea's software can also be used to help design other types of gene expression chips. "You have the Affymetrix chip and then you have the clone spotting chips," Burke explained. "When we're doing a product in Affymetrix mode we generally design sequence sets for them to pick oligos from. These tools basically design the regions that are assayed on the chip when it's used in Affymetrix mode."

Alternatively, when the software is applied to clone-spotting chips, such as those produced by Molecular Dynamics or Synteni, it selects optimal clones. Pangea's product "basically does the chip design," Burke said. "It can retool the older style of fragment EST databases, combine that with full-length knowledge, and turn that into the newer type of chip expression sets. So one of the things the software does is retool for new expression technologies."

Ultimately, Pangea's software produces a set of instructions to tell the vendor what goes onto the chip. "Different vendors have different formats, so if you're designing an Affymetrix chip, the output of our software is the actual Affymetrix format that goes into their chip design software," Burke elaborated. "There are different stages of the design process. We do the sequence-set design for the chip. Affymetrix does the final layout. Basically we provide everything up to Affymetrix's format of the chip."

Custom arrays made easier

To ensure that its software would produce results useful to Affymetrix, Burke continued, Pangea actually tested the prod-uct against the chipmaker's sys-tems. As a result, the company addressed a critical problem that pharmaceutical companies faced: putting data into the correct Affymetrix format was causing bottlenecks, Burke said.

For example, he said, Pangea managed to save a lot of time last year for its first chip-design customer, Roche Bioscience. "Roche was attempting to design gene-family chips for Affymetrix, and it was taking them several months. Once we used our software, the design process took approximately a day," Burke claimed. He contended that not only does the software have the potential to save customers large amounts of time and resources, but the quality and capacity of the final chip design is better. "Our software does a lot of the mundane things automatically, so entries on the chip are much cleaner, leaving more room because you're not polluting the chip with a lot of noninform-ative sequence," he said.

Asked about other chip-design customers, Burke called the projects with Hoechst and Roche "the only two collaborations we can talk about yet."

--Adrienne Burke

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